TY - JOUR
T1 - Poxvirus vectored cytomegalovirus vaccine to prevent cytomegalovirus viremia in transplant recipients
T2 - A phase 2, randomized clinical trial
AU - TRIPLEX VACCINE Study Group
AU - Aldoss, Ibrahim
AU - la Rosa, Corinna
AU - Baden, Lindsey R.
AU - Longmate, Jeffrey
AU - Ariza-Heredia, Ella J.
AU - Rida, Wasima N.
AU - Lingaraju, Chetan Raj
AU - Zhou, Qiao
AU - Martinez, Joy
AU - Kaltcheva, Teodora
AU - Dagis, Andy
AU - Hardwick, Nicola
AU - Issa, Nicolas C.
AU - Farol, Len
AU - Nademanee, Auayporn
AU - Al Malki, Monzr M.
AU - Forman, Stephen
AU - Nakamura, Ryotaro
AU - Diamond, Don J.
AU - Haddad, Esther Arbona
AU - Pandit, Alisha
AU - Drake, Jennifer
AU - Duarte, Lupe
AU - Morrison, Thomas
AU - Paris, Tania
AU - Slape, Cynthia
AU - Palmer, Joycelynne
AU - Araujo, Gloria
AU - Lobo, Yadira
N1 - Publisher Copyright:
© 2020 American College of Physicians
PY - 2020/3/3
Y1 - 2020/3/3
N2 - Background: Triplex vaccine was developed to enhance cytomegalovirus (CMV)-specific T cells and prevent CMV reactivation early after hematopoietic stem cell transplant (HCT). Objective: To determine the safety and efficacy of Triplex. Design: First-in-patient, phase 2 trial. (ClinicalTrials.gov: NCT02506933) Setting: 3 U.S. HCT centers. Participants: 102 CMV-seropositive HCT recipients at high risk for CMV reactivation. Intervention: Intramuscular injections of Triplex or placebo were given on days 28 and 56 after HCT. Triplex is a recombinant attenuated poxvirus (modified vaccinia Ankara) expressing immunodominant CMV antigens. Measurements: The primary outcomes were CMV events (CMV DNA level ≥1250 IU/mL, CMV viremia requiring antiviral treatment, or end-organ disease), nonrelapse mortality, and severe (grade 3 or 4) graft-versus-host disease (GVHD), all evaluated through 100 days after HCT, and grade 3 or 4 adverse events (AEs) within 2 weeks after vaccination that were probably or definitely attributable to injection. Results: A total of 102 patients (51 per group) received the first vaccination, and 91 (89.2%) received both vaccinations (46 Triplex and 45 placebo). Reactivation of CMV occurred in 5 Triplex (9.8%) and 10 placebo (19.6%) recipients (hazard ratio, 0.46 [95% CI, 0.16 to 1.4]; P = 0.075). No Triplex recipient died of nonrelapse causes during the first 100 days or had serious AEs, and no grade 3 or 4 AEs related to vaccination were observed within 2 weeks after vaccination. Incidence of severe acute GVHD after injection was similar between groups (hazard ratio, 1.1 [CI, 0.53 to 2.4]; P = 0.23). Levels of long-lasting, pp65-specific T cells with effector memory phenotype were significantly higher in Triplex than placebo recipients. Limitation: The lower-than-expected incidence of CMV events in the placebo group reduced the power of the trial. Conclusion: No vaccine-associated safety concerns were identified. Triplex elicited and amplified CMV-specific immune responses, and fewer Triplex-vaccinated patients had CMV viremia.
AB - Background: Triplex vaccine was developed to enhance cytomegalovirus (CMV)-specific T cells and prevent CMV reactivation early after hematopoietic stem cell transplant (HCT). Objective: To determine the safety and efficacy of Triplex. Design: First-in-patient, phase 2 trial. (ClinicalTrials.gov: NCT02506933) Setting: 3 U.S. HCT centers. Participants: 102 CMV-seropositive HCT recipients at high risk for CMV reactivation. Intervention: Intramuscular injections of Triplex or placebo were given on days 28 and 56 after HCT. Triplex is a recombinant attenuated poxvirus (modified vaccinia Ankara) expressing immunodominant CMV antigens. Measurements: The primary outcomes were CMV events (CMV DNA level ≥1250 IU/mL, CMV viremia requiring antiviral treatment, or end-organ disease), nonrelapse mortality, and severe (grade 3 or 4) graft-versus-host disease (GVHD), all evaluated through 100 days after HCT, and grade 3 or 4 adverse events (AEs) within 2 weeks after vaccination that were probably or definitely attributable to injection. Results: A total of 102 patients (51 per group) received the first vaccination, and 91 (89.2%) received both vaccinations (46 Triplex and 45 placebo). Reactivation of CMV occurred in 5 Triplex (9.8%) and 10 placebo (19.6%) recipients (hazard ratio, 0.46 [95% CI, 0.16 to 1.4]; P = 0.075). No Triplex recipient died of nonrelapse causes during the first 100 days or had serious AEs, and no grade 3 or 4 AEs related to vaccination were observed within 2 weeks after vaccination. Incidence of severe acute GVHD after injection was similar between groups (hazard ratio, 1.1 [CI, 0.53 to 2.4]; P = 0.23). Levels of long-lasting, pp65-specific T cells with effector memory phenotype were significantly higher in Triplex than placebo recipients. Limitation: The lower-than-expected incidence of CMV events in the placebo group reduced the power of the trial. Conclusion: No vaccine-associated safety concerns were identified. Triplex elicited and amplified CMV-specific immune responses, and fewer Triplex-vaccinated patients had CMV viremia.
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U2 - 10.7326/M19-2511
DO - 10.7326/M19-2511
M3 - Article
C2 - 32040960
AN - SCOPUS:85082930490
SN - 0003-4819
VL - 172
SP - 306
EP - 316
JO - Annals of internal medicine
JF - Annals of internal medicine
IS - 5
ER -